Abstract Curcumin is a primary component of the spice turmeric and it's potent anti-inflammatory and anti-oxidant properties have been demonstrated in multiple organ systems. In rodent animal models, curcumin acts primarily on microglia and astrocytes to inhibit pro-inflammatory signaling pathways and in rodent models of stroke, ischemia, and traumatic brain injury it reduces inflammation and levels of reactive oxygen species. Further, rats with cortical injury treated with curcumin have smaller lesions and fewer neurological impairments than those treated with vehicle. However, the promising effects of curcumin have not yet been extensively tested in non-human primate models of brain injury and it is not clear whether curcumin exerts the same biological effect in primate brains as in rodent brains. Data from our laboratory have demonstrated that daily doses of dietary curcumin enhances spatial working memory and motor function in aging monkeys. In addition, preliminary analyses of brain tissue from these monkeys reveal a lower extent of microglial activation and higher synaptic density compared to vehicle-treated monkeys, which is indicative that curcumin decreases age-related neuroinflammation and increases synaptogenesis. Further, in our non-human primate model of cortical injury, we found an immediate inflammatory response following injury as evidenced by an increase in markers for astrogliosis, microglial activation and oxidative stress in peri-lesional cortical areas that was related to severity of motor impairment. Therefore, this proposal seeks to test the hypothesis that curcumin administration enhances recovery of fine motor function after focal cortical injury in aging rhesus monkeys by reducing post-injury levels of inflammation and oxidation, thus producing a more permissive environment for neuronal recovery and reorganization. We will employ our well-characterized model of non-human primate cortical injury and administer curcumin after injury. Patterns, rates, and magnitudes of recovery of fine motor function and levels of inflammatory biomarkers in the blood and cerebrospinal fluid will be evaluated after cortical injury in curcumin and non-curcumin groups. After recovery has plateaued, cortical electrophysiology and c-fos immediate early gene activation will be used to evaluate recovery-mediated cortical remapping in perilesional motor and premotor cortices. Immunohistochemical labeling and ultrastructural analyses of these cortices will be used to quantify markers of oxidative stress, inflammation, astrocyte and microglial function, neuronal-glial interactions, excitatory-inhibitory synaptic balance and neurite growth. Moreover, single cell in vitro electrophysiological experiments will examine the physiology and detailed structure of pyramidal neurons in perilesional motor areas that underlie recovery. Together, these data will unveil the functional and structural changes associated with the inflammatory response and reorganization that support curcumin-induced recovery of function after cortical injury in the NHP, and provide the validation and the mechanistic basis for human clinical trials with curcumin.